Intestinal Permeability in Irritable Bowel Syndrome With and Without Comorbid Conditions: Results From the European DISCOvERIE Cohort
Year: 2026
Type: article
Study design: Observational Study
Abstract: BACKGROUND: Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction often accompanied by psychiatric and/or somatic comorbidities. Intestinal-barrier dysfunction has been implicated in IBS pathophysiology. However, the contribution of psychiatric and somatic comorbidities to intestinal permeability remains unclear. We aimed to assess intestinal permeability in a large multicentric cohort of IBS patients with and without psychiatric and/or somatic comorbidities, compared with disease controls, and healthy subjects. METHODS: IBS patients and disease controls were recruited across nine European centres. Small intestinal and colonic permeabilities were assessed using the lactulose-mannitol-sucralose urinary excretion test. Urinary sugar concentrations were quantified by gas chromatography-mass spectrometry. Analyses were adjusted for relevant clinical and lifestyle confounders. RESULTS: The lactulose/mannitol (L/M) ratio, but not the percentage of sucralose (%S), was significantly increased in IBS patients (N = 418) compared with disease controls (N = 200), regardless of IBS subtype or sex. Notably, the increased L/M in IBS patients was primarly driven by a significant decrease in mannitol excretion. IBS patients with psychiatric or combined psychiatric and somatic comorbidities showed a higher L/M than their corresponding disease control groups. However, L/M values did not differ between IBS patients with and without comorbidities. Substantial between-centre variability in L/M ratios awas observed. DISCUSSION: Small intestinal, but not colonic, permeability, as reflected by an elevated L/M ratio, is increased in IBS patients. These alterations seem to be related to the presence of IBS per se rather than to comorbid conditions. Interestingly, substantial geographic variability was observed, which may reflect environmental or population-related factors influencing barrier function. Further investigations are needed to better understand the clinical relevance of these findings.
DOI: 10.1002/ueg2.70301
Authors: Alice Rustichelli, Juan Manuel Garcia‐Illarramendi, Javier Santos, Ana Maria González‐Castro, Magnus Simrén, Irina Midenfjord, Amanda Rodriguez‐Urrutia, Elba Expósito, Beatriz Lobo, Jose Alegre‐Martin, Miriam Almirall, Jesús Castro‐Marrero, Ramon Sanmartin‐Sentañes, Jan Tack, Florencia Carbone, Lukas Van Oudenhove, Maaike Van Den Houte, Liene Bervoets, Sybren Rinckhout, Daisy Jonkers, Michelle Bosman, Maria Raffaella Barbaro, Giovanni Barbara, Istvan Bitter, Eva Jekkel, Andreas Reif, Mareike Aichholzer, Carmen Uckermark, Alejandro Arias Vasquez, Dan Lucian Dumitrascu, Andrei‐Vasile Pop, Kristin Verbeke, Carmen Alonso‐Cotoner, Ricard Farré
Institutions: KU Leuven, Vall d'Hebron Institut de Recerca, Vall d'Hebron Hospital Universitari, Universitat Autònoma de Barcelona, Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, University of Gothenburg, Centro de Investigación Biomédica en Red de Salud Mental, Centro de Investigación Biomédica en Red, Maastricht University Medical Centre, University of Bologna, Semmelweis University, Goethe University Frankfurt, University Hospital Frankfurt, Radboud University Medical Center, Donders Institute for Brain, Cognition and Behaviour, Iuliu Hațieganu University of Medicine and Pharmacy
Language: English
Subfield: Gastroenterology
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $2,930
OpenAlex ID: W7225136741